This invention relates to novel 1-(3-methoxybenzyl)-3-substituted thiourea compounds and lipid and oil compositions supplemented with such compounds having enhanced oxidative stability.
Natural lipids and oils are used in pharmaceutical preparations, food products, cosmetics, and various industrial products such as lubricants, coatings, inks, paints, plastics and the like. Such lipids are subject to oxidative degradation which can affect color, odor, viscosity, and lubricity characteristics thereof, adversely affecting the quality of the commercial products containing such lipids. In the food, cosmetics and pharmaceutical industries, maintaining high quality color and odor of oils and other lipids is important to avoiding oxidation-induced rancidity which is affected by factors such as the oxygen concentration, light and heat, as well as the degree of unsaturation of the lipid or oil, and the amount of natural or synthetic antioxidants present therein. Biodegradable lipids, oils and derivatives thereof used as cutting lubricants are recognized to be adversely affected by heat-induced oxidation.
Meadowfoam (Limnanthes alba) seed oil has been demonstrated to be highly stable to oxidation. It is more oxidatively stable than other vegetable oils. Although the identity of the compound(s) responsible for exceptional oxidative stability of meadowfoam seed oil is heretofore unknown, mixing meadowfoam seed oil with other oils imparts enhanced oxidative stability to the resulting mixtures. (Isbell, T. A., Abbott, T. A. and Carlson, K. D., 1999, xe2x80x9cOxidative Stability Index of Vegetable Oils in Binary Mixtures with Meadowfoam Oil,xe2x80x9d Ind. Crops Prod. 9(2): 115-123). Several minor constituents in meadowfoam seed oil which either diminish oxidative stability or impart small increases in oxidative stability of meadowfoam seed oil are known, however. (Abbott, T. P. and Isbell, T. A., 1998, Abstracts of the 89th American Oil Chemist""s Society Annual Meeting and Expo, Chicago, Ill., May 10-13, p 66). Refined meadowfoam seed oil (and other refined seed oils and vegetable oils) exhibit reduced oxidative stability as a result of the refining process. After processing, meadowfoam seed oil has been shown to contain glucolimnanthin, a glucosinolate, and its degradation products 3-methoxyphenyl actetonitrile, 3-methoxybenzyl isothiocyanate and 3-methoxybenzaldehyde. (Vaughn, S. F., Boydston, R. A. and Mallory-Smith, C. A., 1996, xe2x80x9cIsolation and Identification of (3-Methoxyphenyl) Acetonitrile as a Phytotoxin from Meadowfoam (Limnanthes alba) Seedmeal,xe2x80x9d J. Chem. Ecol. 22, 1939-1949). Glucosinolates have been shown to have little or no antioxidant effects. (Plumb, G. W., Lambert, N., Chambers, S. J., Wanigatunga, S., Heaney, R. K., Plumb, J. A., Aruoma, O. I., Halliwell, B. and Miller, N. J., 1996, xe2x80x9cAre Whole Extracts and Purified Glucosinolates from Cruciferous Vegetables Antioxidants?xe2x80x9d Free Rad. Res. 25, 75-86). When added to refined meadowfoam seed oil at levels from about 0.1% to 1.0%, the other compounds exhibit only small to moderate antioxidative effects, at best.
Thiourea has been shown to possess antioxidative activity in oils (Kajimoto and Murakami Nippon Eiyo, Shokuryo Gakkaishi 51(4):207-212, 1998; Chemical Abstract 129:188538); but thiourea is not very soluble in oils. The oxidative stability of ester-based synthetic lubricants (i.e., not vegetable oils) stabilized with amine antioxidants has been shown to be enhanced with specific thioureas (Chao T. S. and Kjonaas, M., xe2x80x9cSome Synergistic Antioxidants for Synthetic Lubricants,xe2x80x9d Amer. Chem. Soc. Preprints, Div. Pet. Chem. 27(2):362-379, 1982). Camenzind and Rolf, Eur. Pat. Appl. EP 91-810474, Chemical Abstract 117:30273, show that certain acylated thioureas are able to increase the oxidative stability to lubricants and hydraulic fluids. Vegetable oils may be stabilized by other alkyl- and aryl-substituted thioureas that are not plant derived, as well (Martin, G. D., xe2x80x9cStabilization of Fatty Acid Compounds,xe2x80x9d 1939, U.S. Pat. No. 2,154,341).
Mono- and di-substituted thiourea compounds also have been described in U.S. Pat. Nos. 2,662,096, 3,852,348 and 3,991,008. Migirab et al., xe2x80x9cIsothiocyanates, thioureas and Thiocarbamates Extracted from Pentadiplandra brazzeanna,xe2x80x9d Phytochem. 16(11): 1719-1721, (1977), disclose methoxy-substituted aromatic thioureas, such as N,Nxe2x80x2-bis[(4-methoxyphenyl)methyl]-thiourea (CAS #22313-70-8) and N,Nxe2x80x2-di(4-methoxybenzyl)thiourea, which were isolated in extracts from Pentadiplandra brazzeana. 
Properties beneficial for commercial applications of lipid antioxidants include antioxidant activity in oils, thermal stability, low toxicity and lipid solubility. If the antioxidant will be employed in a sunscreen formulation for the skin and or hair, UVA and UVB absorbence activities of the antioxidant are also a benefit. Further, a thorough scientific characterization of the antioxidant compounds should include an elemental analysis, as well as NMR and IR spectral data.
There is a need for antioxidant compounds and compositions, especially natural antioxidants or derivatives thereof, that are soluble in lipids and oils, that are capable of imparting oxidative stability thereto when added at low concentrations, that exhibit thermal stability, that are not toxic and/or that absorb UVA and UVB wavelengths of sunlight.
Antioxidant compounds within the present invention are capable of imparting oxidative stability to lipids and/or oils when added at low concentrations, and are soluble in lipids and oils, exhibit thermal stability, are not toxic and/or absorb UVA and/or UVB wavelengths of sunlight. 1,3-di(3-methoxybenzyl)thiourea, for example, appears to have many of the qualities that are beneficial for an effective lipid antioxidant.
We have now unexpectedly discovered that excellent oxidative stability may be imparted to lipids and oils by compounds of the formula I: 
wherein R is a C1-C20 linear or branched alkyl, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, hexyl, octyl, decyl, nonyl, dodecyl, and the like, C5-C7 cycloalkyl, such as cyclopentyl, cyclohexyl or cycloheptyl and the like, hydroxy- or -alkoxy-substituted C5-C7 cycloalkyl, C1-C20 linear or branched alkenyl, such as propenyl, butenyl or octadecenyl and the like, C5-C7 cycloalkenyl, C6-C7 aryl, such as phenyl or benzyl and the like, hydroxy- or alkoxy-substituted C6-C7 aryl, such as hydroxyphenyl, methoxyphenyl, ethoxyphenyl, hydroxybenzyl, methoxybenzyl or ethoxybenzyl and the like, benzoyl or hydroxy- or alkoxy-substituted benzoyl. Among compounds of the formula I, a presently preferred compound is 1,3-di(3-methoxybenzyl) thiourea, that is a compound of such formula I where R is a 3-methoxybenzyl moiety. An amount of a compound of formula I sufficient to impart oxidative stability to a lipid or oil (or compositions containing such lipids or oils) is from about 0.01 wt. % to about 5.0 wt. % based on the total weight of the lipid or oil.
The present invention also provides oxidatively stable lipid compositions comprising from about 95 wt. % to about 99.99 wt. % of a base lipid or oil and between about 0.01 wt. % and about 5.0 wt. %, more preferably between about 0.05 wt. % and 2.0 wt. %, and most preferably between about 0.1 wt. % and 1.0 wt. % of a compound of formula I. Lipids or oils of the present invention containing between about 3 wt. % and about 5 wt. % or more of a substituted thiourea compound of formula I, based on the total weight of the base lipid or oil composition, may be used as xe2x80x9cconcentratesxe2x80x9d and conveniently added to processed seed oils or other lipids in need of enhanced oxidative stability to provide a lipid or oil composition of the present invention.
The present invention further provides a method for imparting oxidative stability to a base lipid or oil composition in need of enhanced oxidative stability, comprising the step of supplementing a base lipid or oil with an amount of a compound of formula I sufficient to impart enhanced oxidative stability to the base lipid or oil.
Presently preferred compounds of formula I are 1,3-di(3-methoxybenzyl)thiourea; 1-(3-methoxybenzyl)-3-ethyl-2-thiourea; 1-(3-methoxybenzyl)-3-propyl-2-thiourea; 1-(3-methoxybenzyl)-3-hexyl-2-thiourea; 1-(3-methoxybenzyl)-3-octadecyl thiourea; 1-(3-methoxybenzyl)-3-dodecyl-2-thiourea; 1-(3-methoxybenzyl)-3-octyl thiourea; 1-(3-methoxybenzyl)-3-(1-propenyl)thiourea; 1-(3-methoxybenzyl)-3-(4-hydroxyphenyl)-2-thiourea; 1-(3-methoxybenzyl)-3-benzyl thiourea; 1-(3-methoxybenzyl)-3-(3-methoxyphenyl)-2-thiourea and 1-(3-methoxybenzyl)-3-(4-methoxybenzoyl)thiourea. 1,3-di(3-methoxybenzyl)thiourea, which the inventors have identified as a significant natural antioxidant in meadowfoam seed oil, and in meadowfoam seed oil by-products, is a particularly preferred compound of the invention. 1,3-di(3-methoxybenzyl)thiourea from meadowfoam seed oil or meadowfoam seed oil by-products, or synthesized directly, appears to have many of the qualities that are beneficial for an effective lipid antioxidant.
It also has been surprisingly found that compounds of formula I, in combination with a benzylamine compound such as N-substituted benzylamines, exhibit a synergistic oxidative stabilizing effect in lipids and oils. Various naturally-occurring lipids and oils, such as seed oils and vegetable oils, contain benzylamine compounds. In these cases, the synergistic effect may be obtained by supplementing such a base lipid or oil with a compound of formula I and, optionally, with an exogenously added benzylamine compound in an amount sufficient to impart yet a further enhancement in oxidative stability. Thus, another aspect of the present invention entails lipid compositions comprising (i) a compound of formula I and (ii) a benzylamine or N-substituted benzylamine compound to impart enhanced oxidative stability.
The present invention may be understood more readily by reference to the following detailed description of the preferred embodiments of the invention, and to the examples included therein.
In one of its aspects, the present invention entails 1-(3-methoxybenzyl)-3-substituted thiourea compounds of the formula I: 
wherein R is selected from the group consisting of C1-C20 linear or branched alkyl; C5-C7 cycloalkyl; alkoxy-substituted C5-C7 cycloalkyl; hydroxy-substituted C5-C7 cycloalkyl; C1-C20 linear or branched alkenyl; C5-C7 cycloalkenyl; C6-C7 aryl; hydroxy-substituted C6-C7 aryl; alkoxy-substituted C6-C7 aryl; benzoyl; hydroxy-substituted benzoyl; and alkoxy-substituted benzoyl. In a particularly preferred embodiment, the substituted aryl moiety is a 3-hydroxy-substituted or 3-alkoxy-substituted aryl compound.
In another of its aspects, the present invention entails a lipid composition with enhanced oxidative stability comprising from about 95 wt. % to about 99.99 wt. % of a base lipid and from about 0.01 wt. % to about 5.0 wt. %, more preferably between about 0.05 wt. % and 2.0 wt. %, and still more preferably about 0.1 wt. % to about 1.0 wt. %, of a 1-(3-methoxybenzyl)-3-substituted thiourea compound of the formula I: 
wherein R is selected from the group consisting of C1-C20 linear or branched alkyl; C5-C7 cycloalkyl; hydroxy- or alkoxy-substituted C5-C7 cycloalkyl; C1-C20 linear or branched alkenyl; C5-C7 cycloalkenyl; C6-C7 aryl; hydroxy- or alkoxy-substituted C6-C7 aryl; benzoyl; and hydroxy- or alkoxy-substituted benzoyl.
In a further of its aspects, the present invention entails a method of enhancing the oxidative stability of a lipid, comprising the step of combining a lipid with an oxidative stability-enhancing amount of a compound of the formula I: 
wherein R is selected from the group consisting of C1-C20 linear or branched alkyl; C5-C7 cycloalkyl; hydroxy- or alkoxy-substituted C5-C7 cycloalkyl; C1-C20 linear or branched alkenyl; C5-C7 cycloalkenyl; C6-C7 aryl; hydroxy- or alkoxy-substituted C6-C7 aryl; benzoyl; and hydroxy- or alkoxy-substituted benzoyl.
The compounds of the present invention may be added to essentially any lipid in which the compounds of the invention are soluble to augment the oxidative stability of such lipid. The term xe2x80x9clipidxe2x80x9d as used herein includes vegetable oils, seed oils, triglycerides, waxes of triglycerides, and phospholipids. Among the lipids that may be supplemented with amounts of the compounds of the present invention to impart enhanced oxidative stability are vegetable oil, jojoba oil, sunflower oil, milkweed oil, peanut oil, corn oil, cottonseed oil, safflower oil, soybean oil, rapeseed (canola) oil, palm oil, olive oil, jojoba wax ester and lecithin. As used herein, the phrase xe2x80x9cbase lipid,xe2x80x9d xe2x80x9cbase oilxe2x80x9d or equivalent phrase means a lipid or oil to which a compound of formula I has not been exogenously added.
As used herein, xe2x80x9cC1-C20 linear or branched alkylxe2x80x9d shall include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, 2-methyl-pentyl, 3-methyl-penyl, hexyl, octyl, decyl, dodecyl, and the like. The term xe2x80x9cC5-C7 cycloalkylxe2x80x9d shall include cyclopentyl, cyclohexyl and cycloheptyl. The term xe2x80x9chydroxy- or alkoxy-substituted C5-C7 cycloalkylxe2x80x9d shall include cyclopentyl, cyclohexyl and cycloheptyl moieties that are substituted with an hydroxy, methoxy, ethoxy, or propoxy group or the like. The term xe2x80x9cC6-C7 arylxe2x80x9d shall include phenyl and benzyl. The term xe2x80x9chydroxy- or alkoxy-substituted C6-C7 arylxe2x80x9d shall include phenyl and benzyl moieties that are substituted with a hydroxy, methoxy, ethoxy or propoxy group or the like. The term xe2x80x9cC1-C20 linear or branched alkenylxe2x80x9d shall include propenyl, butenyl, pentenyl, hexenyl, octenyl, decenyl, dodecenyl, octadecenyl and the like. The term xe2x80x9cC5-C7 cycloalkenylxe2x80x9d shall include cyclopentenyl, cyclohexenyl and cycloheptenyl. The term xe2x80x9chydroxy- or alkoxy-substituted benzoylxe2x80x9d shall include a benzoyl moiety, as that term is defined in the art, that is substituted with an hydroxy, methoxy, ethoxy, or propoxy group or the like.
By use of the phrase xe2x80x9cenhanced oxidative stability,xe2x80x9d xe2x80x9caugmented oxidative stabilityxe2x80x9d or an equivalent phrase, it is meant that a lipid composition of the invention has an increased ability to inhibit oxidation as measure by the Oxidative Stability Index (OSI) and/or by the Oxidative Stability by Rotating Pressure Vessel (RBOT) test disclosed herein, as compared to the base lipid or oil (i.e., one not supplemented with an exogenously added compound of formula I). It is presently preferred that a lipid or oil composition of the invention exhibit an OSI and/or RBOT value at least 10% greater, more preferably at least 100% greater, and most preferably at least about 200% greater or more than the OSI or RBOT value of the base lipid or base oil composition to which it is compared, when the OSI test is carried out at a temperature between about 110xc2x0 C. and about 130xc2x0 C., and the RBOT test is carried out under the conditions described herein.
The phrase xe2x80x9ccombining a lipid or oil with an oxidative stability-enhancing amount of a compound of formula Ixe2x80x9d as used herein includes the addition of a compound of formula I directly to the lipid or oil, as well as the addition to the lipid or oil of compounds that react therein to form a compound of formula I, for example 3-methoxybenzylamine and an isothiocyanate compound of the formula II (defined hereinbelow), preferably in a one to one ratio.
Compounds of the formula I may be synthesized by reacting 3-methoxybenzylamine and an appropriately selected isothiocyanate compound of the formula II Sxe2x95x90Cxe2x95x90Nxe2x80x94R, wherein R is defined the same as for compounds of formula I. The reaction may be carried out by slowly adding the isothiocyanate to an aqueous solution of 3-methoxybenzylamine, preferably under a nitrogen atmosphere. The thiourea product of the reaction, which is a compound of formula I, may be recovered and purified by mixing the reaction products with a solvent that is not miscible with water but one that is a solvent for the thiourea, such as methylene chloride, chloroform, toluene or diethyl ether. The water layer may or may not be acidified to enhance separation and recovery of the thiourea compound of the invention. The thiourea, dissolved in the solvent layer, can be drawn off from the water layer, dried and the resulting crude thiourea purified by recrystallization in an appropriate solvent, such as ethanol. See the examples set forth hereinbelow. See also, generally, the procedure of Moore and Crossley, Organic Synthesis 2, 617-618 (note 4).
The reactants, 3-methoxybenzylamine and an appropriate isothiocyanate compound as defined above, may be obtained commercially or may be synthesized by routine methods known in the art, and the resultant product compounds of formula I may be readily isolated by routine methods well-known to those having ordinary skill in the art. Suitable isothiocyanate reactants for synthesizing compounds of the present invention may be obtained as well-known in the art from degradation of glucosinolates present in seed oils and other lipids. In an aqueous solution containing the enzyme thioglucosidase, glucosinolate compounds are degraded into isothiocyanates and other degradation products. See, Vaughn et al., 1996, xe2x80x9cIsolation and Identification of (3-Methoxyphenyl) Acetonitrile as a Phytotoxin from Meadowfoam (Limnanthes alba) Seedmeal,xe2x80x9d J. Chem. Ecol. 22, 1939-1949; and C. VanEtten and H. Tookey, 1983, Glucosinolates, pp. 15-30 in M. Rechcigl (ed.) xe2x80x9cNaturally Occurring Food Toxicants,xe2x80x9d CRC Press, Boca Raton, Fla. The isothiocyanate fraction of the glucosinolate breakdown products, thus, may be isolated and reacted with 3-methoxybenzylamine, as described above, to provide compounds of the present invention. Approximately 100 glucosinolate compounds have been identified in plants from 11 different plant families including mustard, rapeseed, cabbage, garlic mustard and crambe (S. F. Vaughn, 1999, xe2x80x9cGlucosinolates as Natural Pesticides in Biologically Active Natural Products: Agrochemicals,xe2x80x9d H. G. Cutler and S. J.Cutler, Eds, CRC Press, Boac Raton, Fla.) Oils isolated from glucosinolate containing plants are normally deodorized by steam sparging to remove volatile compounds, which include isothiocyanates and amines. Thus, a variety of isothiocyanate compounds and benzylamine compounds may be obtained from the waste distillation products generated in the process of purifying such oils, and employed as reactants in synthesizing compounds of the present invention.
3-methoxybenzylamine may be purchased commercially, or may be isolated from meadowfoam oil, by extraction into an immiscible acidified aqueous layer which is separated from the oil, washed with a nonpolar solvent, treated with a base to lower pH, and the amine extracted into an immiscible solvent. The 3-methoxybenzylamine compound may be further purified by crystallization from ethanol or similar solvent and/or purified by reverse-phase HPLC using a C18 column, eluting with a gradient starting at 100% methanol and proceeding to about 80% methanol:20% chloroform. The peak containing 3-methoxybenzylamine may be identified by its retention time on the HPLC column in comparison to the retention time for a known standard sample of 3-methoxybenzylamine. Other natural amines may be purchased commercially, or may be similarly extracted from natural sources, and purified with reference to known standard samples and/or identified by standard chemical methods for identification of amines (e.g., chromatography, infrared spectroscopy, mass spectroscopy, elemental analysis, nuclear magnetic resonance analysis and the like).
The oxidative stability of a lipid, with and without addition of a compound of the present invention, may be determined by procedures that are described in the literature. See, for example, K. Tian and P. Dasgupta, Anal. Chem. 71, 1692-98 (1999).
A presently preferred method of determining oxidative stability of lipids and oils employs the Oxidative Stability Index (OSI), which determines the oxidative stability of an oil by passing air through a sample under stringent temperature control. (Firestone, Oxidative Stability Index (OSI): Official Methods of Recommended Practices of the American Oil Chemists"" Society (AOCS), 4th Ed. American Oil Chemists Society, Champaign, Ill., AOCS Official Method Cd 12b-92, 1993.) In this method, a stream of air is passed through the oil sample, which aids in the rapid degradation of the triglyceride into volatile organic acids. The air stream flushes the volatile acids from the oil into a conductivity cell containing water where the acids are solubilized. These acids, once dissolved in the water solution, disassociate into ions, thus changing the conductivity of the water. Therefore, a continuous measure of the conductivity of the cell by computer will indicate when a rapid rise in the conductivity occurs that corresponds to the induction point, oxidative failure of the sample. The time to the induction point is the OSI time. An AOCS standard method has been recently developed and a collaborative study has also been published (Jebe et al., J. Am. Oil Chem. Soc. 70, 1055-61 (1993)), demonstrating that the OSI method has good reproducibility among samples and laboratories. Saturated fatty acid methyl ester (FAME) standards commercially available from Alltech Associates (Deerfield, Ill.) may be used to calibrate the OSI determinations.
OSI determinations may be performed on an oxidative stability instrument manufactured by Omnion (Rockland, Mass.) using the AOCS method described in the above-disclosed Firestone reference. Lipid or oil samples may be run at 110xc2x0 C. and FAMEs may be tested at 90xc2x0 C., with air flow set at 35 kPa with a resulting velocity of about 140ml/min. A presently preferred method for determining OSI values is described by T. A. Isbell et al., xe2x80x9cOxidative Stability Index of Vegetable Oils in Binary Mixtures with Meadowfoam Oil,xe2x80x9d Industrial Crops and Products 9, 115-123 (1999).
Another presently preferred method of determining oxidative stability of lipids and oils employs the Oxidative Stability by Rotating Pressure Vessel (RBOT) test. In this test, oxidative stability, determined according to the ASTM D2272-98 test method (ASTM, 2001, xe2x80x9cStandard Test Method for Oxidation Stability of Steam Turbine Oils by Rotating Pressure Vessel,xe2x80x9d in Book of Standards, Vol. 05.01., American Society for Testing and Materials, West Conshohocken, Pa.), measures the time for oxygen pressure to decrease in a closed stainless steel vessel containing a lipid or oil when heated with a copper coil catalyst. Oxygen taken up by the lipid or oil during the reaction is an indication of oil degradation.
Compounds of formula I may be conventionally mixed with a suitable lipid or oil and solubilized at concentrations up to 3.0%-5.0% or more. It is presently contemplated that concentrations of a compound of formula I between about 0.1% and 1.0% are sufficient to provide up to about 2-fold to 10-fold enhancement in oxidative stability of a base lipid or oil in need of enhanced oxidative stability. However, lipids or oils of the present invention containing up to 3.0%-5.0% of a compound of formula I are useful as xe2x80x9cconcentratesxe2x80x9d that can be conveniently diluted up to 30- to 50-fold or more with a base lipid in need of enhanced oxidative stability. The base composition of such a concentrate may itself be a lipid or oil such as a seed oil or vegetable oil or a food grade solvent. Moreover, a compound of formula I, optionally in combination with an amine compound, such as 3-methoxybenzylamine, may be provided in an oil-in-water emulsion or a water-in-oil emulsion, or the like. The emulsions are presently contemplated to be especially useful as additives to biodegradable cutting lubricants, such as canola oil, soybean oil, vegetable oil estolyte, or other cutting lubricants, to enhance the oxidative stability of such lubricants.
In presently preferred embodiments of the lipid or oil compositions of the invention, the base lipid or oil is supplemented with an effective amount of a compound of formula I, e.g., a concentration of between about 0.1% and 1.0%, as well as a benzylamine compound present in an amount sufficient to augment the oxidative stability imparted by the compound of formula I. The amount of a benzylamine compound to be added to a lipid or oil composition of the invention may be determined by observing increases in OSI and/or RBOT values as a function of amount of the benzylamine compound added. While a base lipid or oil may inherently contain an amine compound, additional amounts of an amine compound, preferably 3-methoxybenzylamine, may be added to a lipid or oil that has been supplemented with a compound of formula I to increase the oxidative stability of such a lipid or oil composition of the present invention. The amount of such an amine compound to be added to a lipid or oil composition of the invention to achieve a synergistic anti-oxidation effect may be determined empirically by adding predetermined amounts of the amine compound to aliquots of the lipid or oil composition containing a compound of formula I and measuring the increase in OSI and/or RBOT value(s) obtained.
The following nonlimiting examples further describe and illustrate the methods for the preparation of the compounds and compositions of the invention, as well as the scientific characterization of synthesized compounds and the testing of synthesized compounds to determine their antioxidant activities, lipid solubility, thermal stability, toxicity and/or ability to absorb UVA and/or UVB light wavelengths. The examples are intended to be merely illustrative of the present invention, and not limiting thereof in either scope of spirit. Those of skill in the art will readily understand that variations of certain of the conditions and/or steps employed in the procedures described in the examples can be used to prepare and test these compounds and compositions.
All of the materials and equipment employed in the examples, and generally employed to make and test the compounds and compositions of the present invention, are commercially available from sources known by those of skill in the art. 3-methoxybenzyl isothiocyanate, 3-methoxyphenyl isothiocyanate and 4-methoxybenzoyl isothiocyanate were obtained from Transworld Chemicals (Rockville, Md.). Octadecylamine hydrochloride, dodecylamine, octylamine, allyl isothiocyanate, 3-methoxybenzyl amine, benzyl isothiocyanate and most of the other chemicals employed in the examples were obtained from Fisher Scientific (Pittsburgh, Pa.), and generally were reagent grade. Crude meadowfoam seed oil was obtained as approximately 50% oil in hexane solutions, and refined meadowfoam seed oil was obtained from the Fanning Corporation (Chicago, Ill.). Refined jojoba oil was obtained from Purcell Jojoba International, LLC (Avila Beach, Calif.), and high oleic sunflower oil was obtained from International Flora Technologies (Gilbert, Ariz.). Refined, bleached and deodorized soybean oil was obtained from Archer Daniels Midland (Decatur, Ill.), and refined milkweed oil was obtained from the United States Department of Agriculture (Peoria, Ill.).
Unless otherwise stated, all percentages described in the examples are weight percentages (wt. %).
Unless otherwise stated, Oxidative Stability Index (OSI) values were determined on 5.00xc2x10.05 g lipid or oil samples in triplicate according to AOCS Official Method Cd 12b-92 (AOCS, 1993) at 90xc2x0 C., 110xc2x0 C. and/or 130xc2x0 C. on an oxidative stability instrument manufactured by Omnion (Rockland, Mass.). Details of the procedure have been published by Isbell et al., xe2x80x9cOxidative Stability Index of Vegetable Oils in Binary Mixtures with Meadowfoam Oil,xe2x80x9d Ind. Crops Prod. 9, 115-123 (1999). When compounds of the present invention were added to the lipid or oil sample being tested, the compounds (0.1 % to 1.0% by weight) were added to the test lipid or oil (20 g) and dissolved or dispersed at room temperature before triplicate 5.00 g samples of lipid or oil with an added compound of the invention were weighed into the OSI test tube.